Method and apparatus for determining attention deficit hyperactivity disorder (ADHD) medication dosage and for monitoring the effects of ADHD medication on people who have ADHD using complementary tests

ABSTRACT

A method for determining the appropriate dosage of a medication to treat Attention Deficit Hyperactivity Disorder (ADHD) in an individual who has ADHD. The method comprises sampling the peripheral skin temperature of left and right like extremities of an individual during a predetermined time interval when the individual is in a sensory deprived state to provide respective left and right sampled peripheral skin temperature data; processing the sampled peripheral skin temperature data; processing the sampled peripheral skin temperature data including filtering, differentiation, and conversion to the frequency domain to derive spectral signatures whose magnitudes are indicative of the level of ADHD manifestation. The effectiveness of the medication is calculated by comparison to predetermined threshold values.

FIELD OF THE INVENTION

[0001] This invention relates in general to technique for monitoring theeffectiveness of medication taken to treat Attention DeficitHyperactivity Disorder (ADHD) and more particularly to a technique andapparatus for measuring and objectively analyzing an individual'speripheral temperature variability to determine values indicative of thelevel of manifestation of ADHD.

BACKGROUND OF THE INVENTION

[0002] ADHD is the most common neurobehavioral disorder of childhood aswell as among the most prevalent health conditions affecting school-agedchildren. Between 4% and 12% of school age children (several millions)are affected. $3 billion is spent annually on behalf of students withADHD. Moreover, in the general population, 9.2% of males and 2.9% offemales are found to have behavior consistent with ADHD. Upwards of 10million adults may be affected.

[0003] ADHD is presently a difficult disorder to diagnose. The coresymptoms of ADHD in children include inattention, hyperactivity, andimpulsivity. ADHD children may experience significant functionalproblems, such as school difficulties, academic underachievement, poorrelationships with family and peers, and low self-esteem. Adults withADHD often have a history of losing jobs, impulsive actions, substanceabuse, and broken marriages. ADHD often goes undiagnosed if not caughtat an early age and affects many adults who may not be aware of thecondition. ADHD has many look-alike causes (family situations,motivations) and co-morbid conditions (depression, anxiety, and learningdisabilities) are common.

[0004] Diagnosis of ADHD currently involves a process of eliminationusing written and verbal assessment instruments. However, there is noone objective, independently validated test for ADHD. Various objectivetechniques have been proposed but have not yet attained widespreadacceptance. These include:

[0005] 1. The eye problem called convergence insufficiency was found tobe three times more common in children with ADHD than in other childrenby University of California, San Diego researchers.

[0006] 2. Infrared tracking to measure difficult-to-detect movements ofchildren during attention tests combined with functional MRI imaging ofthe brain were used by psychiatrists at McLean Hospital in Belmont,Mass. to diagnose ADHD in a small group of children (Nature Medicine,Vol. 6, No. 4, April 2000, Pages 470-473).

[0007] 3. Techniques based on EEG biofeedback for the diagnoses andtreatment of ADHD are described by Lubar (Biofeedback andSelf-Regulation, Vol. 16, No. 3, 1991, Pages 201-225).

[0008] 4. U.S. Pat. No. 6,097,980, issued Aug. 1, 2000, inventorMonastra et al, discloses a quantitative electroencephalographic processassessing ADHD.

[0009] 5. U.S. Pat. No. 5,913,310, issued Jun. 22, 1999,inventor Brown,discloses a video game for the diagnosis and treatment of ADHD.

[0010] 6. U.S. Pat. No. 5,918,603, issued Jul. 6, 1999, inventor Brown,discloses a video game for the diagnosis and treatment of ADHD.

[0011] 7. U.S. Pat. No. 5,940,801, issued Aug. 17, 1999, inventor Brown,discloses a microprocessor such as a video game for the diagnosis andtreatment of ADHD.

[0012] 8. U.S. Pat. No. 5,377,100, issued Dec. 27, 1994, inventors Popeet al., discloses a method of using a video game coupled with brain wavedetection to treat patients with ADHD.

[0013] 9. Dr. Albert Rizzo of the Integrated Media Systems Center of theUniversity of Southern California has used Virtual Reality techniquesfor the detection and treatment of ADHD.

[0014] 10. U.S. Pat. No. 6,053,739, inventors Stewart et al., disclosesa method of using a visual display, colored visual word targets andcolored visual response targets to administer an attention performancetest.

[0015] U.S. Pat. No. 5,377,100, issued Dec. 27, 1994, inventors Pattonet al., discloses a system and for managing the psychological state ofan individual using images.

[0016] U.S. Pat. No. 6,117,075 Barnea discloses a method of measuringthe depth of anesthesia by detecting the suppression of peripheraltemperature variability.

[0017] There are several clinical biofeedback and physiologic monitoringsystems (e.g. Multi Trace, Bio Integrator). These systems are used byprofessional clinicians. Although skin temperature spectralcharacteristics have been shown to indicate stress-related changes ofperipheral vasomotor activity in normal subjects, there has been nodisclosure of use of variations in skin-temperature response to assistin diagnosing ADHD. (See: Biofeedback and Self-Regulation, Vol. 20, No.4, 1995).

[0018] As stated above, the primary method for diagnosing ADHD is theuse of a bank of written and verbal assessment instruments designed toassess the children for behavioral indicators of criteria established byAmerican Medical Association (AMA) as described in the Diagnostic andStatistics manual—IV (DSM-IV). Psychiatrists, psychologists, schoolpsychologists and other licensed practitioners administer theseassessment instruments. In some cases those individuals who meet DSM-IVcriteria for ADHD diagnosis are prescribed a drug such as Ritalin.Behavioral observations of the patient while on Ritalin are conducted toassess the impact of prescribed medication. However, clearly establishedcriteria for evaluating the impact of specific medications e.g., Ritalinand specific dosages are lacking. It would be advantageous forphysicians to have access to clearly established physiologic criteria,which could be measured, to determine if a specific medication at aspecific dosage effectively addressed the underlying physiologicparameter, which was indicative of ADHD.

[0019] There is thus a need for a simple, inexpensive, and reliableobjective technique for determining the effectiveness of the medicationand appropriate dosage taken to counteract ADHD by an individual who hasADHD.

SUMMARY OF THE INVENTION

[0020] According to the present invention, there is provided a solutionto the problems discussed above.

[0021] According to a feature of the present invention, there isprovided a method for determining the appropriate dosage of a medicationto treat Attention Deficit Hyperactivity Disorder (ADHD) in anindividual who has ADHD comprising:

[0022] (a) sampling the peripheral skin temperature of left and rightlike extremities of an individual during a predetermined time intervalwhen the subject is in a sensory deprived state to provide respectiveleft and right sampled peripheral skin temperature data;

[0023] (b) a first processing of at least one of said left and rightsampled peripheral skin temperature data providing conversion to thefrequency domain to derive a first spectral signature having magnitudevalues;

[0024] (c) a second processing of both said left and right sampledperipheral skin temperature data to derive temporally correlateddifferential data;

[0025] (d) said second processing further filtering said differentialdata with a high pass filter to produce filtered differential data withnear d. c. components removed;

[0026] (e) said second processing lastly providing conversion to thefrequency domain of said filtered differential data to derive a secondspectral signature having magnitude values;

[0027] (f) a third processing of the said first spectral signature forthe determination of the level of manifestation of ADHD by comparison toa predetermined first threshold value;

[0028] (g) a fourth processing of the said second spectral signature forthe determination of the level of manifestation of ADHD by comparison toa predetermined threshold value; and

[0029] (h) a fifth processing wherein an assessment of the bi-modalquality of the results of the third and fourth processing is made, toprovide a final determination of one of the following threepossibilities:

[0030] (i) a various level of dosage change;

[0031] (ii) dosage level is adequate;

[0032] (iii) there is noise in the data.

ADVANTAGEOUS EFFECT OF THE INVENTION

[0033] The invention has the following advantages.

[0034] 1. A device and technique for objectively determining theeffectiveness of the medication and appropriate dosage taken tocounteract ADHD by an individual who has ADHD which is simple,inexpensive and reliable.

BRIEF DESCRIPTION OF THE DRAWINGS

[0035]FIG. 1 is a diagrammatic view illustrating use of an embodiment ofthe present invention.

[0036]FIG. 2 is a perspective view showing in greater detail theembodiment of FIG. 1.

[0037]FIGS. 3a and 3 b are block diagrams of portions of a systemincorporating the present invention.

[0038]FIGS. 4, 5 and 6 are graphical views useful in explaining thepresent invention.

[0039]FIG. 7 is a diagram of an example of using the threshold θ_(g) andthe patient's computed aggregation statistic Θ_(m) to diagnose thepresence or absence of ADHD and determine the suggested drug dosage.

[0040]FIG. 8 is a block diagram of the second processing of the presentinvention.

[0041]FIG. 9 is a table of the parameter values selected for the filterin accordance with the second processing of the present invention.

[0042]FIG. 10 is a graph of the filter parameters in accordance with thesecond processing of the present invention.

[0043]FIG. 11 is a plot of the spectral response of the filter of FIGS.9 and 10.

[0044]FIG. 12 is of sample of the second processing resultant spectralsignature plots from two sessions, showing differing response.

DETAILED DESCRIPTION OF THE INVENTION

[0045] According to the present invention, it has been found thatsignatures of ADHD are hidden in fluctuation of the temperature of theskin as measured at the extremities such as at the fingertips. Ingeneral, as an individual's stress level increases the peripheralvasculature constricts and often the person's blood pressure increases.As the blood vessels in the body constrict, blood flow is restricted.This is most easily monitored in the extremities such as the fingers,because the blood vessels in the extremities are small and veryresponsive to Sympathetic Nervous System (SNS) innervations. A directresult of decreased blood flow to the blood vessels in the extremitiesis a decrease in the peripheral temperature of the extremities.Conversely, as an individual's stress level decreases and relaxationoccurs, the blood vessels expand, allowing blood to flow in a lessrestricted manner. As the blood flow to the vessels in the extremitiesincreases the peripheral temperature of the extremities increases. It issuspected that when a subject with ADHD is subjected to sensorydeprivation such as being made to look at a blank screen or an obscuredimage for a period of time in an inactive state, the lack of stimulationincreases and there tends to be a shift in the subject's physiologicreactivity indicative of an increase in their stress level. As theirstress level increases their blood vessels contract and the peripheraltemperature of their extremities decreases. Biofeedback practitionershave long used measurement of hand temperature to help subjects managetheir physiology by controlling blood flow to the extremities. Theliterature reports that reduced blood flow to the brain is frequentlyfound in patients with ADHD.

[0046] In addition to peripheral skin temperature and peripheral skintemperature variability there are other known physiologic measures whichare known (or potential) indicators of stress such as; bilateraltemperature variability, heart rate, heart rate variability, muscletension (excessive and chronic, measured via surfaceelectromyography—sEMG), bilateral muscle tension imbalance, galvanicskin response (i.e., electro dermal response—EDR), eye saccades, bloodoxygen (SpO₂), salivary IGA, electroencephalography (EEG), peripheralblood flow (measured via photoplethismography—PPG), and peripheral bloodflow variability (PPG).

[0047] As shown in FIG. 1, a subject 10 is sitting on a chair 12 at atable 13 watching a screen 14. The screen 14 is used to block any visualstimulus from disturbing the subject 10. Since said visual stimulus maybe in the subject's peripheral vision, the screen 14 illustrated in FIG.1 may be larger, for example a blank wall or corner of a room In anotherembodiment, which is not shown, the subject can wear a pair oftranslucent glasses, goggles or eye mask for the same purpose. Thesedevices may be internally illuminated for uniformity and to furtherminimize the propensity to self-stimulate with mental images, which iseasier to do with a dark state before one's eyes. For the same reason,the subject is instructed to not close their eyes, except to blink. Thesubject 10 is wearing a set of headphones 20. The headphones 20 can beconnected to a sound-generating device not shown. The headphones 20 canbe used to block out ambient noise or to produce a white noise intendedto reduce or eliminate the audio stimulus from the environment duringthe test. The subject is at rest in an inactive state and sensorydeprived. The fingertip 16 of subject 10 is inserted into a temperaturerecording module 18 along groove 17, where the skin temperature ismeasured via a sensor 22 (shown in FIG. 2). A second temperature sensormodule 28 is connected to the temperature recording module 18 via acable 29. The second temperature sensor module 28 is used to sample theskin temperature of the subject's 10 other hand's fingertip and includesgroove 34 and temperature sensor 36. In another embodiment of thepresent invention, to prevent the possibility of sensor to skin contactvariability due to finger movement in the grooves 17; 34 and against thesensors 22; 36, the groove 17 corresponding sensor 22, and the secondtemperature sensor module 28 are replaced with discrete temperaturesensors, both wired to the temperature recording module, and held inplace against their respective fingertips by tape, or any such availablemeans. The sensor glove disclosed in U.S. patent application Ser. No.09/892,824, filed on Jun. 27, 2001, Docket no. 82479, may also bepreferably used.

[0048] As shown in FIG. 2, the temperature recording module 18 alsoincludes an on/off switch 24, and a display 26, which is disabled duringa session. The temperature recording module 18 can have an internalpower supply, such as a battery 30, or an external low voltage powersupply port 32 for an external low voltage power supply (not shown),such as used for a telephone. The temperature recording module 18 can beconnected to an external data processor (not shown) via a cable 27 (suchas a USB or RS 232 cable), optical fiber, or wireless transmittingdevice such as an RF or IR link (not shown).

[0049] In a further embodiment, a slot 118 is provided to accept amemory card 119 to allow the transport of the recorded temperature data.In these embodiments, the data processing and analysis is done at adifferent location, for example at a computer, a PDA device, or throughthe Internet. In another embodiment, the electronics to do the dataprocessing and analysis is contained in the temperature recordingmodule, with the results transported by any of the aforesaid means. Thedisplay 26 may also show the result, in addition to indicating thatfingertip temperatures are being sensed correctly prior to the start ofa session. In this self-contained configuration, the system may be madeupgradeable by providing bi-directionality across the data transportpath.

[0050] In FIG. 1, the fingertip temperatures are being recorded duringan interval when the subject 10 has been asked to sit quietly for aperiod of about 10 minutes. Not shown is the recording sensor for theother fingertip. Fig. w shows an embodiment for recording said otherfingertip. As shown in FIG. 3a, the temperature data is sampled by 41 ata time interval that provides 32 samples per second per sensor, creatingat least two sets, left and right, of n temperature data, which arestored in storage 42.

[0051] First Processing

[0052] In the preferred embodiment of the present invention, a firstprocessing is next carried out on these data. As shown in FIG. 3a, thisprocessing begins with window blocking 43, continuing Fourier transform44, Magnitude calculation 45, Mrange calculation 46, aggregation stepblock 47, Threshold comparison step block 48, previously determinedthreshold θ_(g) 49, and threshold comparison result block 50. The methodof determining dosage is further expanded in FIG. 3b.

[0053] Now further referring to FIG. 3a, in block 43, the n samples aredivided into z windows Of m samples, each group corresponding to a giventime window of width Δt (˜32-64 sec) equally spaced in time (˜50 sec)across the entire baseline data collection time 600 seconds. The datafrom each window is then passed through a Fast Fourier Transform (FFT)algorithm 44 producing 2^(m−1) data points spaced equally in frequencyspace for each window. The values are complex numbers having form

FFT(f _(m))=A(f _(m))+B(f _(m))i

[0054] where i is the $\sqrt{- 1}.$

[0055] The Phase Φ(f_(m)) is then found from the equation$\begin{matrix}{{\Phi_{l}\left( f_{m} \right)} = {{Tan}^{- 1}\left( \frac{B\left( f_{m} \right)}{A\left( f_{m} \right)} \right)}} & \text{(1.0)}\end{matrix}$

[0056] and the Magnitude M(f_(m)) from $\begin{matrix}{{M_{l}\left( f_{m} \right)} = \sqrt{{B\left( f_{m} \right)}^{2} + {A\left( f_{m} \right)}^{2}}} & (1.1)\end{matrix}$

[0057] In the equations 1.0 and 1.1 the subscript l refers to the factthat a separate signal is extracted for each hand so the subscript is lfor data extracted from the left-hand data and r for data from the righthand. FIG. 4 graphically illustrates the temperature signal during onewindow for a normal subject and a person diagnosed with ADHD.

[0058]FIGS. 5 and 6 graphically illustrate the magnitude transform forthe data corresponding with a subject with ADHD and normal subject.These spectral signatures of this first processing undergo dramaticchanges essentially changing from a hyperbolic curve to a flat response.In FIG. 6, the magnitude range is substantially less than shown in FIG.5, indicating ADHD manifestation.

[0059] Raw Data

[0060] The raw data T_(k,l)(t) is the temperature taken from hand l at afingertip 16 as shown in FIG. 1, during the 10-minute session. Thesessions were taken over a period of weeks. Some subjects had as few as2 sessions and some as many as 5 sessions. k is used to represent thesession.

[0061] Referring again to FIG. 3a:

[0062] Windows

[0063] The data for each session were divided into a series of windows(block 43) prior to performing the Fourier Transform operation. Call thewindow width w. In this analysis, the window width was 64 seconds andthere were 10 windows spaced at 50-second intervals (the windowsoverlap) across the 600 sec baseline spanning the range of 100-500 sec,other values of w can be used. The window number in a session isreferred to with the letter j. For each window a FFT algorithmcalculates the Fourier Transform F(f). The Magnitude and Phase of thistransform are defined as given above.

[0064] In block 46 the range of magnitude variation during a window iscalculated using equation (1.2) below where f_(max) and f_(min) are thefrequencies where the Magnitude is the greatest and the leastrespectively (note the dc component at frequency zero is excluded).

M _(range) =[M(f _(max))−M(f _(min))]  (1.2)

[0065] In a further embodiment of this method, other statistics from aFourier Transform, calculated from the quantities denoted above asA(f_(m)), B(f_(m)), θ(f_(m)), and M(f_(m)) may be used. In addition tousing Fourier Transforms, another embodiment may use statistics derivedfrom a Wavelet transform of data or other filtering of the data (as inStrang, G. and Nguyen, T. (1996), Wavelets and Filter Banks,Wellesley-Cambridge Press, Wellesley, Mass.).

[0066] Aggregation of Samples

[0067] During this first processing, windowing the data for conversionto the frequency domain results in multiple first spectral signatureslike those shown in FIGS. 5 and 6, which must be combined. MRange valuesfor all windows are aggregated in block 47. There are z windows fromeach hand from each session. The first step is to choose an aggregationstatistic, which can be the mean, median, variance, or other statistic,which is an aggregate of the computed M_(range) values in each windowfor each session and each hand. Other statistics that may be used foraggregation include the standard deviation, range, interquartiledistance, skewness, kurtosis, Winsorized mean and variance, and robustestimates of mean and variance. Equations below are given foraggregating the mean and the variance. The mean magnitude range for theleft hand during session k is found from equation 2.0. where z is thenumber of windows in the session. $\begin{matrix}{{\text{<}M_{k,l}\text{>}} = \frac{\sum\limits_{j = 1}^{z}\quad \left\lbrack {{M\left( f_{\max} \right)}_{j} - {M\left( f_{\min} \right)}_{j}} \right\rbrack}{z}} & \text{(2.0)}\end{matrix}$

[0068] And the corresponding variance is: $\begin{matrix}{{\text{<}{Var}_{k,l}\text{>}} = \frac{\sum\limits_{j = 1}^{z}\quad \left\{ {\left\lbrack {{M\left( f_{\max} \right)}_{j,l} - {M\left( f_{\min} \right)}_{j,l}} \right\rbrack - {\text{<}M_{k,l}\text{>}}} \right\}^{2}}{z - 1}} & (2.1)\end{matrix}$

[0069] Combining these session means and variances over both hands andall the sessions s that a subject attended gives an aggregated mean μand aggregated variance. $\begin{matrix}{\mu = \frac{\sum\limits_{k = 1}^{s}{\sum\limits_{l = 1}^{2}{\text{<}M_{k,l}\text{>}}}}{2s}} & \text{(2.2)} \\{\text{<var>} = \frac{\sum\limits_{k = 1}^{s}{\sum\limits_{l = 1}^{2}{var}_{k,l}}}{2s}} & \text{(2.3)}\end{matrix}$

[0070] Further embodiments of this aggregation step of the firstprocessing include using the data from only one hand—either the lefthand, the right hand, or the dominant hand (and if the subject isambidextrous, the dominant hand would be defined as the average of bothhands). In addition, future embodiments may not require averaging ofseveral sessions, but selecting only one session for use or using aweighted combination of each session's results.

[0071] Diagnostic Indicators

[0072] Referring again to FIG. 3a, the normalized group diagnosticthreshold indicator θ_(g) was established previously from theaggregation statistics determined using data from a large group ofsubjects having similar demographic characteristics-block 49, and canvary based upon gender, age or weight. This group diagnostic thresholdθ_(g) is calculated statistically from group temperature variabilitydata using methods described in U.S. patent application Ser. No.09/597,610, filed Jun. 20, 2000.

[0073] When the subject's measured aggregation statistic Θ_(m) (fromequation 2.2 or 2.3) block 47 is less than the group thresholdθ_(g)-block 49, the test 48 indicates the subject has ADHD. When themeasured aggregation Θ_(m) statistic is greater than the predeterminedthreshold θ_(g), the test indicates no manifestation of ADHD-block 50and no medication is required-block 51. The same threshold θ_(g) may beused for all subjects or θ_(g) may have a value that is different fordifferent groups based on gender or age.

[0074] Determination of Proper Dosage

[0075] Now referring to FIG. 3b, based upon the computed value of theaggregation statistic Θ_(m)-block 60 and the predetermined thresholdvalue θ_(g)-block 62, a mathematical formula-block 66 is used to computethe proper dosage-block 68 for subjects who are diagnosed as havingADHD. This mathematical formula may also include demographicinformation-block 64, including gender, age and weight. An example ofsuch a mathematical formula is the following:

Dosage=100×(θ_(g)−Θ_(m)−1)+100×gender

[0076] where the dosage is in milligrams of a drug, and where gender iscoded as 0 if the patient is female and 1 if the patient is male. Forexample, if θ_(g)=10 and Θ_(m)=8, and the patient is male, the exampleformula would call for a dosage of 100×(10−8−1)+100×1=200 milligrams ofthe drug.

[0077] Medication Effectiveness Indicator

[0078] If the prescribed medication is effective in correcting the ADHD,then the measured physiologic diagnostic indicator Θ_(m) (as defined byequation 2.2 or 2.3) would be expected to come within the normal rangeand exceed θ_(g) during the time the patient is medicated.

[0079] Thus, to determine if the dosage is effective, the patient willbe re-tested according to the following procedure as illustrated in FIG.3b. The subject will take the prescribed dosage of the medication andthen wait a certain period of time-block 70. The subject's peripheraltemperature will be measured and Θ_(m) will be calculated-block 72. Thistime period can range from the minimum time it takes for the drug tobecome effective after ingestion, to the maximum length of time the drugis effective after ingestion, to the maximum length of time the drug iseffective after ingestion. Ideally, the test will occur at a time periodequal to the drug's half-life in the body (note that a profile of thedrug's efficacy over time could be acquired by repeated, evenly spacedtesting by the methods of the present invention, from the time ofingestion, to the cessation of effectiveness). Next, compare the newlycomputed Θ_(m) value to threshold θ_(g)-block 74. If value of Θ_(m)moves to the non-ADHD region (above threshold θ_(g)), it is concludedthat the medication and dosage are appropriate-block 78. If value ofΘ_(m) remains in the ADHD region (below threshold Θ_(g)), it isconcluded that a larger dosage is needed block 76. The dosage can beincreased according to best medical practices. This procedure blocks70-78 can be repeated until appropriate medication and dosages aredetermined such that the patient's Θ_(m) value, when re-tested, is inthe non-ADHD region (above threshold θ_(g)).

[0080] Because a patient's physiology can change over time, theeffective dosage may change over time as well. Thus, the patient needsto be monitored during the treatment period in accordance with the bestmedical practices. One such monitoring scheme, which should be followedduring the entire time the patient is taking the drug, is toperiodically re-test the patient. The interval between these periodictests can for example, be one month to one year. The monitoringprocedure involves repeating blocks 70-78. In one embodiment of theinvention, the initial dosage found-block 78 could be replaced with anenhancement in which, if Θ_(m) exceeds θ_(g) by a large amount, thedosage is decreased, while if Θ_(m) exceeds θ_(g) by a small amount,then the proper dosage has been found.

[0081] Complementary Analysis Method

[0082] In the preferred embodiment of the present invention, a secondprocessing of the data allows the assessment of the bi-modality of thespectral energy of peripheral temperature variability where, forexample, when ADHD is manifesting, the just described first processingdetermines a decrease of spectral energy below around 0.005 Hz. and thesecond processing next described determines an increase in bilaterallydifferential spectral energy 0.03 Hz. The opposite bi-modality should beseen with adequate medication.

[0083] Referring to FIG. 8, using the same sampled data from datastorage 42 of FIG. 3a, the first step in the second processing is tosubtract each data value of one hand from the temporal companion data ofthe other hand, producing a differential value 100 for each sampleperiod. Next, a Butterworth High-pass Infinite Impulse Response Filter102 is applied to the differential data, producing a roll-offcharacteristic, increasingly attenuating towards frequency zero.Removing the near-dc components in this way allows for greaterdiscrimination of the area in the frequency domain of interest,empirically determined to center around 0.030 Hz., with the describedfiltering.

[0084] As there may be differences in software to perform thistransform, the application used is identified here as the DaDisp™application by DSP Development Corporation. FIG. 9 is a table of theparameter values selected for the Butterworth Highpass IIR filter 102.FIG. 10 is a graph of the Butterworth Highpass IIR filter parameters.FIG. 11 is a plot of the spectral response for the Butterworth HighpassHR filter of FIGS. 9 and 10.

[0085] The resultant high-passed differential data are then passedthrough a Fast Fourier Transform (also by DaDisp™) 104, to derive thespectral signature, which is then compared 108 against a pre-determinednorm 106, generating result 110 of FIG. 8, in like manner to 47 through50 of FIG. 3a for the first processing. FIG. 12 illustrates actualsample resultant plots of the spectral content of the filteredleft/right hand temperature differential, showing a magnitude differencebetween an ADHD subject 114 and non-ADHD subject 115, of ratio 3 to 1.Here, as in the first processing, the effect of proper medication dosagefor an ADHD subject is to make this processing spectral signature closerin magnitude to that seen with a non-ADHD subject. Test/adjust iterationfor determination of proper dosage, as described in the first processingreferencing FIG. 3b, includes the evaluation of this second processingresult.

[0086] Thusly, similar to the analysis method of the first processing,the just described second processing provides a measurement means formedication effectiveness, that is, the magnitude of a final spectralsignature. But with two differences: firstly, the portion of thespectrum of interest is centered around 0.03 Hz., and secondly, themagnitude of the spectral signature decreases in a proportion to theeffectiveness of the medication.

[0087] It is therefore concluded here, considering the aforesaiddetermination, that very slow peripheral temperature variability is notsimply suppressed in ADHD manifestation, but rather, moves upward infrequency, and becomes markedly bilaterally differential in nature.

[0088] The mechanism for this ADHD manifestation is thought to be thelessening of the slower, common control of the left and right peripheraltemperatures by the autonomic nervous system, resulting in the controlof temperature at said periphery being more localized and therefore lesscorrelated to each other.

[0089] Multiplicity of Tests

[0090] A well known statistical principle is that the variability of theaverage of multiple tests is less than the variability of one test.Therefore, an advantage of effective, additional, concurrent testing,e.g. the combined analyses of the same session data, is increasedaccuracy.

[0091] Noise Detection

[0092] A key advantage of the present invention that combines the firstprocessing and the just described second analysis processing is theability to distinguish external noise from true physiological function.External noise will manifest as increased spectral content, which canoccur anywhere in the spectrum, including within the regions ofinterest. It may be anywhere from broadband to very frequency-specific.Such noise is usually difficult to discern unless the specific frequencyor bandwidth is known, which is not the case with such measurements.

[0093] The present invention provides a means for noise detection due tothe nature of vasomotor activity. Peripheral temperatures are ultimatelycontrolled in all cases, thereby producing the same total spectralenergy on average. The present invention provides complimentary tests ofthis feature of physiology, that if the magnitude of energy is less inone spectral region, the case in the first processing when ADHD ismanifesting, the magnitude of energy is greater in the other spectralregion, the case in the second processing, The matched opposites ofthese results indicate that the subject is receiving adequatemedication. This bi-modal spectral characteristic will not be seen withnoise since it can only be additive. Noise in the data is therebyidentifiable. This is accomplished at block 112 of FIG. 8, whichinversely compares result block 50 of FIG. 3a to result 110 of FIG. 8.(Note that this does not mean that the noise can be removed; the test isinvalidated. The course of action is re-testing and/or the removal ofthe source of noise at the testing site).

[0094] According to the present invention then, the now described fistand second processing result in the following possible test outcomes:

[0095] 1) a various level of dosage change

[0096] 2) dosage level adequate

[0097] 3) there is noise in the data

[0098] The invention has been described in detail with particularreference to certain preferred embodiments thereof, but it will beunderstood that further study could indicate refinements andoptimizations, ad that such variations and modifications can be effectedwithin the spirit and scope of the invention.

PARTS LIST

[0099] subject

[0100]10 chair

[0101]12 table

[0102]13 screen

[0103]14 fingertip

[0104]16 digit groove

[0105]17 temperature recording module

[0106]20 headphones

[0107]22 sensor

[0108]24 on/off switch

[0109]26 display

[0110]27 cable

[0111]28 temperature sensor module

[0112]29 cable

[0113]30 battery

[0114]32 external low voltage power supply port

[0115]34 groove

[0116]36 temperature sensor

[0117]41 temperature sampling circuit

[0118]42 data storage

[0119]43 window blocking

[0120]44 Fourier transform

[0121]45 magnitude calculation

[0122]46 Mrange calculation

[0123]47 aggregation block

[0124]48 threshold comparison block

[0125]49 previously determined threshold θ_(g) block

[0126]50 decision block

[0127]51 no medication required block 51

[0128]60 computed value of aggregation statistic Θ_(m)

[0129]62 threshold value θ_(g)

[0130]64 demographics

[0131]66 mathematical formula to determine initial dosage

[0132]68 initial dosage

[0133]70 ingest drug and wait

[0134]72 re-test step

[0135]74 compare new Θ_(m) to threshold θ_(g)

[0136]76 increase dosage

[0137]78 proper dosage

[0138]100 differential derivation block

[0139]102 filter block

[0140]104 Fourier Transform block

[0141]106 previously determined norm

[0142]108 comparison block

[0143]110 result

[0144]112 noise detection block

[0145]114 ADHD subject spectral plot

[0146]115 non-ADHD subject spectral plot

[0147]118 memory card slot

[0148]119 memory card

What is claimed is:
 1. A method for determining the appropriate dosageof a medication to treat Attention Deficit Hyperactivity Disorder (ADHD)in an individual who has ADHD comprising: (a) sampling the peripheralskin temperature of left and right like extremities of an individualduring a predetermined time interval when the subject is in a sensorydeprived state to provide respective left and right sampled peripheralskin temperature data; (b) a first processing of at least one of saidleft and right sampled peripheral skin temperature data providingconversion to the frequency domain to derive a first spectral signaturehaving magnitude values; (c) a second processing of both said left andright sampled peripheral skin temperature data to derive temporallycorrelated differential data; (d) said second processing furtherfiltering said differential data with a high pass filter to producefiltered differential data with near d. c. components removed; (e) saidsecond processing lastly providing conversion to the frequency domain ofsaid filtered differential data to derive a second spectral signaturehaving magnitude values; (f) a third processing of the said firstspectral signature for the determination of the level of manifestationof ADHD by comparison to a predetermined first threshold value; (g) afourth processing of the said second spectral signature for thedetermination of the level of manifestation of ADHD by comparison to apredetermined threshold value; and (h) a fifth processing wherein anassessment of the bi-modal quality of the results of the third andfourth processing is made, to provide a final determination of one ofthe following three possibilities: (i) a various level of dosage change,(ii) dosage level is adequate; (iii) there is noise in the data.
 2. Themethod of claim 1 wherein said level of dosage change of the said finaldetermination is calculated by comparisons of the magnitudes of saidfirst and second spectral signatures with respective predetermined firstand second threshold values using mathematical equations that canresolve anywhere within a gradient of ADHD manifestation for each saidcomparison, such that said level of dosage change is a function of howgreat is the difference between respective said magnitudes and saidthreshold values.
 3. The method of claim 1 wherein the said comparisonsmust correlate by indicating substantially the same level of dosagechange for such said final determination to be acceptable.
 4. The methodof claim 3 wherein the absence of a substantial correlation determinesthat there is noise in the data.
 5. The method of claim 1 wherein incomparing said first spectral signature magnitude values to saidpredetermined first threshold value, if said first spectral signaturemagnitude value is greater than said predetermined first thresholdvalue, the proper dosage of medication is partially determined, and ifsaid second spectral signature magnitude value is lesser than saidpredetermined second threshold value, proper dosage of medication istotally determined.
 6. The method of claim 1 wherein said left and rightlike extremities sampled are the pair of said individual's two hands ortwo feet.
 7. The method of claim 6 wherein one or more digits of each ofsaid pair are sampled during said sampling.
 8. The method of claim 1wherein said left and right extremities sampled are said individual'sears.
 9. The method of claim 1 wherein said differential data is derivedby subtracting one of said left and right sampled data from the other ofsaid left and right sampled data.
 10. The method of claim 1 wherein saidhigh-pass filter used in said filtering is a Butterworth High-PassInfinite Impulse Response (IIR) Filter.
 11. The method of claim 1wherein said second spectral signature has a spectral response ofinterest which is centered around approximately 0.03 Hz.
 12. The methodof claim 1 including a headphone adapted to be worn by the subjectduring said predetermined time interval to block out ambient noise or toreceive white noise to reduce or eliminate audio stimulus from theambient environment during said time interval.
 13. The method of claim12 including a source of white noise coupled to said headphone toprovide white noise during said predetermined time interval.
 14. Themethod of claim 1 including providing glasses or goggles adapted to beworn by the subject during said predetermined time interval to block outor eliminate ambient visual stimulus from the ambient environment duringsaid time interval.
 15. The method of claim 14 including presenting auniformly illuminated visual field to the individual during saidpredetermined time interval to minimize the human propensity toself-stimulate with mental imagery.
 16. The method of claim 1 whereindifferent threshold values are used for each of both genders.
 17. Themethod of claim 1 wherein different threshold values are used for eachof different age groups.
 18. A method of adjusting a medication to treatADHD comprising: administering an initial dosage of a medication to anindividual who has ADHD; after waiting a period of time for themedication to take effect, conducting an analysis of the peripheral skintemperatures of said individual including the processes of sampling,differentiation, filtering, conversion to the frequency domain, andcomparison to predetermined values; and based on said comparison: (a)maintaining said dosage if said comparison is now not indicative ofADHD, or (b) increasing said dosage if said comparison is stillindicative of ADHD.
 19. The method of claim 18 wherein said period oftime is a function of the medication's half-life in a human body. 20.The method of claim 1 including administering a dosage of medication toan individual being tested; repeating at temporally evenly spacedintervals the sampling and first through fifth processing; and producinga profile of the efficacy over time of said medication by tabulating theresults obtained at said temporally evenly spaced intervals.
 21. Themethod of claim 20 including concluding said testing when the resultsindicate that the effect of the ingested medication has ceased. 22.Apparatus for determining the appropriate dosage of a medication totreat Attention Deficit Hyperactivity Disorder (ADHD) in an individualwho has ADHD comprising: a device for sampling the peripheral skintemperature of left and right like extremities of an individual during apredetermined time interval when the subject is in a sensory deprivedstate to provide respective left and right sampled peripheral skintemperature data; and a processor for carrying out: a first processingof at least one of said left and right sampled peripheral skintemperature data providing conversion to the frequency domain to derivea first spectral signature having magnitude values; a second processingof both said left and right sampled peripheral skin temperature data toderive temporally correlated differential data; said second processingfurther filtering said differential data with a high pass filter toproduce filtered differential data with near d. c. components removed;said second processing lastly providing conversion to the frequencydomain of said filtered differential data to derive a second spectralsignature having magnitude values; a third processing of the said firstspectral signature for the determination of the level of manifestationof ADHD by comparison to a predetermined first threshold value; a fourthprocessing of the said second spectral signature for the determinationof the level of manifestation of ADHD by comparison to a predeterminedthreshold value; and a fifth processing wherein an assessment of thebi-modal quality of the results of the third and fourth processing ismade, to provide a final determination of one of the following threepossibilities: a various level of dosage change; dosage level isadequate; there is noise in the data.
 23. The apparatus of claim 22wherein said level of do sage change of the said final determination iscalculated by comparisons of the magnitudes of said first and secondspectral signatures with respective predetermined first and secondthreshold values using mathematical equations that can resolve anywherewithin a gradient of ADHD manifestation for each said comparison, suchthat said level of dosage change is a function of how great is thedifference between respective said magnitudes and said threshold values.24. The apparatus of claim 23 wherein the said comparisons mustcorrelate by indicating substantially the same level of dosage changefor such said final determination to be acceptable.
 25. The apparatus ofclaim 23 wherein the absence of a substantial correlation determinesthat there is noise in the data.
 26. The apparatus of claim 22 whereinin comparing said first spectral signature magnitude values to saidpredetermined first threshold value, if said first spectral signaturemagnitude value is greater than said predetermined first thresholdvalue, the proper dosage of medication is partially determined, and ifsaid second spectral signature magnitude value is lesser than saidpredetermined second threshold value, proper dosage of medication istotally determined.
 27. The apparatus of claim 22 wherein said left andright like extremities sampled are the pair of said individual's twohands or two feet.
 28. The apparatus of claim 27 wherein one or moredigits of each of said pair are sampled during said sampling.
 29. Theapparatus of claim 22 wherein said left and right extremities sampledare said individual's ears.
 30. The apparatus of claim 22 wherein saiddifferential data is derived by subtracting one of said left and rightsampled data from the other of said left and right sampled data.
 31. Theapparatus of claim 22 wherein said high-pass filter used in saidfiltering is a Butterworth High-Pass Infinite Impulse Response (IIR)Filter.
 32. The apparatus of claim 22 wherein said second spectralsignature has a spectral response of interest which is centered aroundapproximately 0.03 Hz.
 33. The apparatus of claim 22 including aheadphone adapted to be worn by the subject during said predeterminedtime interval to block out ambient noise or to receive white noise toreduce or eliminate audio stimulus from the ambient environment duringsaid time interval.
 34. The apparatus of claim 33 including a source ofwhite noise coupled to said headphone to provide white noise during saidpredetermined time interval.
 35. The apparatus of claim 22 includingproviding glasses or goggles adapted to be worn by the subject duringsaid predetermined time interval to block out or eliminate ambientvisual stimulus from the ambient environment during said time interval.36. The apparatus of claim 35 including presenting a uniformlyilluminated visual field to the individual during said predeterminedtime interval to minimize the human propensity to self-stimulate withmental imagery.
 37. The apparatus of claim 22 wherein differentthreshold values are used for each of both genders.
 38. The apparatus ofclaim 22 wherein different threshold values are used for each ofdifferent age groups.